Applying the intervention Complexity Assessment Tool to brief interventions targeting long-term benzodiazepine receptor agonist use in primary care: Lessons learned

Background Benzodiazepine receptor agonists (BZRAs) are often prescribed for long-term use. However, guidelines recommend limiting prescriptions to short-term use (< 4 weeks) to reduce the risk of adverse effects and dependence. A recent systematic review reported that brief interventions targeting long-term BZRA use in primary care (e.g., short consultations, written letters to patients) were effective in helping patients to discontinue BZRA medication. However, the complexity of these interventions has not been examined in detail. This study aimed to apply the intervention Complexity Assessment Tool for Systematic Reviews (iCAT_SR) to brief interventions targeting long-term BZRA use. Methods Two reviewers independently assessed the interventions using the six core iCAT_SR dimensions: organisational level/ category targeted, behaviour targeted, number of intervention components, degree of tailoring, skill level required by those delivering and receiving the intervention. The four optional iCAT_SR dimensions were applied where possible. A scoring system was using to calculate a complexity score for each intervention. Pearson’s correlations were used to assess the relationship between intervention complexity and effect size, as well as the relationship between intervention complexity and number of component behaviour change techniques (BCTs). Inter-rater reliability was calculated using Cohen’s Kappa coefficient. Results Four of the six core iCAT_SR dimensions were applied to the interventions with high inter-rater reliability (Cohen’s Kappa = 0.916). Application of the four optional dimensions was prevented by a lack of detail in study reports. Intervention complexity scores ranged from 8 to 11 (median: 11). There was no relationship detected between intervention complexity and either intervention effect size or number of component BCTs. Conclusions This study adds to the literature on worked examples of the practical application of the iCAT_SR. The findings highlight how more detailed reporting of interventions is needed in order to optimise the application of iCAT_SR and its potential to differentiate between interventions across the full range of complexity dimensions. Further work is needed to establish the validity of applying a scoring system to iCAT_SR assessments. Supplementary Information The online version contains supplementary material available at 10.1186/s12875-022-01775-y.

Intervention target/recipient (which may include individuals, groups of individuals and other entities) "long-term BENZODIAZEPINE users who would be identified by their GPs as suitable to receive a brief intervention aimed at encouraging a reduction in BENZODIAZEPINE intake" Target behaviour and component actions (i.e. whose behaviour the intervention intended to change and what were the component actions involved in that behaviour "change in BENZODIAZEPINE intake between the six-month periods before and after the intervention."

Intervention Group 1: Consultation Group Core dimension
Description of the intervention in the review Judgement Support for judgement 1. Organisational levels and categories targeted by the intervention "…patients were sent a letter inviting them to see their GP for a medication review.." Single category Intervention only targets patients

Behaviour or actions of intervention recipients or participants to which the intervention is . directed
"The main outcome measure was change in BENZODIAZEPINE intake between the six-month periods before and after the intervention."

Single target
Only one behaviour the intervention is targetingbenzodiazepine intake.

Active components included in the intervention, in relation to the comparison
"In this group, 98 patients were sent a letter inviting them to see their GP for a medication review. Before the trial began, the researcher met participating GPs to give guidance on how the consultation should be carried out. Consultations were scheduled to last for 12 min. Written guidelines were produced consisting of information for patients about benzodiazepines, reasons why it might be beneficial to reduce medication and a timetable that could be used to plan withdrawal (see Appendix 1). These guidelines were attached to patients' notes so that the GP could refer to them during the consultation. GPs were allowed discretion as to how the consultation was conducted. Copies of a self-help booklet, entitled Helping you Cope: A Guide More than one component and delivered as a bundle The components of the intervention included a GP consultation, self-help booklet, a leaflet, and a letter. Defined order in the delivery of these interventionsacademic review would precede use of the web-based algorithm, medication review and distribution of PILs to patients.
to Starting and Stopping Tranquillisers and Sleeping Tablets, were supplied by The Mental Health Foundation and given to patients during the consultation, along with a leaflet about sleeping problems. In one practice, the consultation was carried out by the Practice Pharmacist (27 patients) and in another by a Practice Nurse (3 patients)."

. The degree of tailoring intended or flexibility permitted across sites or individuals in applying or implementing the intervention
"GPs were allowed discretion as to how the consultation was conducted."

Moderately flexible
GPs were allowed discretion and could tailor consultations.

The level of skill required by those delivering the intervention in order to meet the intervention's objectives
Before the trial began, the researcher met participating GPs to give guidance on how the consultation should be carried out. Consultations were scheduled to last for 12 min. Written guidelines were produced consisting of information for patients about benzodiazepines, reasons why it might be beneficial to reduce medication and a timetable that could be used to plan withdrawal (see Appendix 1). These guidelines were attached to patients' notes so that the GP could refer to them during the consultation

Intermediate level skills
GPs had to be upskilled in how to carry out the consultations and support BZRA discontinuation .

The level of skill required for the targeted behaviour when entering the included studies by those receiving the intervention, in order to meet the intervention's objectives
Not explicitly stated in the report -high level skills required to undergo successful BZRA discontinuation High level skills High level skills required to undergo BZRA discontinuation .

Optional dimension Description of the intervention in the review
Judgement Support for judgement

The degree of interaction between intervention components, including the independence / interdependence of intervention components
Not outlined unclear/ unable to assess

The degree to which the effects of the intervention are dependent on the context or setting in which it is implemented
Not outlined Unclear/Unable to assess 9. The degree to which the effects of the intervention are modified by recipient or provider factors

Not outlined
Unclear/ Unable to assess

The nature of the causal pathway between the intervention and the outcome it is intended to effect
Not outlined Unclear/Unable to assess Intervention Group 2: Letter Group Core dimension Description of the intervention in the review Judgement Support for judgement

1) Organisational levels and categories targeted by the intervention
"…patients were sent a letter inviting them to see their GP for a medication review.."

2) Behaviour or actions of intervention recipients or participants to which the intervention is directed
"The main outcome measure was change in benzodiazepine intake between the six-month periods before and after the intervention."

Single target
Only one behaviour the intervention is targetingbenzodiazepine intake.

3) Active components included in the intervention, in relation to the comparison
"93 patients were sent an amended version of the letter used in the study by Cormack and colleagues (see Appendix 2). The letter was produced by the research team on practice-headed paper and signed by the patient's usual GP. Patients in the Letter group were not sent the self-help booklet or leaflet"

One component
Letter was the only component of the intervention.
4) The degree of tailoring intended or flexibility permitted across sites or individuals in applying or implementing the intervention "patients were sent an amended version of the letter used in the study by Cormack and colleagues"

Inflexible
No tailoring of letter. Study aims/objectives "to test the effectiveness of direct patient education about drug harms on benzodiazepine therapy discontinuation among community-dwelling adults 65 years and older receiving longterm benzodiazepine therapy" Study outcome(s) "The primary outcome was complete cessation of benzodiazepine use in the 6 months following randomization." Results for secondary outcomes were not included in the paper. Details of intervention/s and the comparison (including usual care) Intervention: "The patient empowerment intervention consisted of an 8-page booklet based on social constructivist learning and self-efficacy theory, and its development and testing have been previously detailed. The intervention comprises a self-assessment component about the risks of benzodiazepine use, presentation of the evidence for benzodiazepine-induced harms, knowledge statements designed to create cognitive dissonance about the safety of benzodiazepine use, education about drug interactions, peer champion stories intended to augment self-efficacy, suggestions for equally or more effective therapeutic substitutes for insomnia and/or anxiety, and stepwise tapering recommendations. Tapering recommendations consist of a visual 21-week tapering protocol showing a picture-based diminishing schedule of full-pill, half-pill, and quarter-pill consumption. The visual schematic for the deprescribing protocol was proposed by consumers during the development and usability testing of the intervention to enable application to any benzodiazepine, regardless of dose. The intervention asks participants to discuss the deprescribing recommendations with their physician and/or pharmacist. The information is included in a letter-size paper handbook, with the language set at a sixth-grade reading level and written in 14-point font to facilitate accessibility to the material. The intervention was personalized according to the participant's pharmacy profile to include the name of the specific benzodiazepine the participants was taking. The intervention was mailed to the intervention group within 1 week of group allocation while the usual care (wait list) group received the educational tool 6 months following group allocation. A full version of the intervention is available in the appendix in the Supplement."

5) The level of skill required by those delivering the intervention in order to meet the intervention's objectives
Control: "The intervention was mailed to the intervention group within 1 week of group allocation while the usual care (wait list) group received the educational tool 6 months following group allocation. " Intervention aim/objectives "The intervention asks participants to discuss the deprescribing recommendations with their physician and/or pharmacist" Intervention deliverer Research team "A full list of pharmacies within 200km of the research centre was obtained through collaboration with the pharmacy chain's headquarters. This list was randomized, and pharmacies were systematically contacted by the research team to assess interest in participating." "All clients meeting study criteria received a recruitment mailing followed by telephone call invitations from their pharmacists. Patients who expressed interest in participating in the study were directed to the study team and screened for eligibility via in-home interviews with a research assistant." "The intervention asks participants to discuss the deprescribing recommendations with their physician and/or pharmacist."" Intervention target/recipient (which may include individuals, groups of individuals and other entities) "The sampling frame for individual participants was a list of all adults 65 years and older receiving long-term benzodiazepine therapy from each participating pharmacy, provided to pharmacists by the central database system of the pharmacy chain. " Target behaviour and component actions (i.e. whose behaviour the intervention intended to "benzodiazepine therapy discontinuation among communitydwelling adults 65 years and older receiving long-term benzodiazepine therapy." change and what were the component actions involved in that behaviour) "discuss the deprescribing recommendations with their physician and/or pharmacist"

Core dimension
Description of the intervention in the review Judgement Support for judgement 1. Organisational levels and categories targeted by the intervention "a direct-to-consumer educational intervention" "The intervention was mailed to the intervention group" Single category Intervention was only targeted at patients.

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"benzodiazepine therapy discontinuation among community-dwelling adults 65 years and older receiving long-term benzodiazepine therapy." "discuss the deprescribing recommendations with their physician and/or pharmacist"

Single target
Only one behaviour being targeted benzodiazepine discontinuation . Study aims/objectives "to assess the effectiveness of minimal intervention delivered by general practitioners in helping chronic users of benzodiazepines to withdraw from their medication, and to determine the psychological sequelae on patients of such intervention" Study outcome(s) Withdrawal from benzodiazepines Change in "psychological distress experienced before and after intervention" Details of intervention/s and the comparison (including usual care) "Patients were allocated by their doctor to receive either minimal intervention, consisting of general practitioner advice on coming off benzodiazepines plus a self-help booklet which patients took away to read, or to receive no intervention: this group acted as controls." "It would have been impossible in a controlled trial to impose rigid guidelines on general practitioners concerning the management of benzodiazepine withdrawal. Instead it was suggested that doctors should outline the risks of benzodiazepines, advise patients to reduce and then stop their medication, and then encourage patients to follow the advice in the self-help booklet. The booklet was divided into two sections, the first giving some basic information about benzodiazepines and the second giving practical advice on stopping, including techniques on coping with fears and anxieties." Intervention aim/objectives "help chronic users to withdraw from their benzodiazepines."

Active components included in the intervention, in relation to the comparison
Intervention deliverer GP -"It would have been impossible in a controlled trial to impose rigid guidelines on general practitioners concerning the management of benzodiazepine withdrawal" Intervention target/recipient (which may include individuals, groups of individuals and other entities) "General practitioners were asked to recruit all chronic benzodiazepine users" "A chronic user was defined as someone who had been on benzodiazepines for at least a year and who took tablets at least three times weekly." Target behaviour and component actions (i.e. whose behaviour the intervention intended to change and what were the component actions involved in that behaviour) Patients "to withdraw from their medication" (benzodiazepines)

Core dimension
Description of the intervention in the review Judgement Support for judgement

Organisational levels and categories targeted by the intervention
"Patients were allocated by their doctor to receive either minimal intervention,…"

Single category
Only the patients are targeted by the intervention.

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"help chronic users to withdraw from their benzodiazepines."

Single target
Only one behaviour targeted -benzodiazepine use.

Active components included in the intervention, in relation to the comparison
"Patients were allocated by their doctor to receive either minimal intervention, consisting of general practitioner advice on coming off benzodiazepines plus a self-help booklet which patients took away to read, or to receive no intervention: this group acted as controls." More than one component as a bundle Intervention included advice from doctor and self-help book to take away.

The level of skill required by those delivering the intervention in order to meet the intervention's objectives
No explicitly mentioned in report -intermediate level skills to support patients in benzodiazepine withdrawal.

Intermediate level skills
Intermediate level skills to support patients in benzodiazepine withdrawal.

The level of skill required for the targeted behaviour when entering the included studies by those receiving the intervention, in order to meet the intervention's objectives
Not explicitly stated in the report -high level skills required to undergo successful BZRA discontinuation High level skills High level skill to undergo benzodiazepine discontinuation successfully.

Judgement Support for judgement 7. The degree of interaction between intervention components, including the independence / interdependence of intervention components
Not outlined Unclear/Unable to assess

The degree to which the effects of the intervention are dependent on the context or setting in which it is implemented
Not outline Unclear/Unable to assess 9. The degree to which the effects of the intervention are modified by recipient or provider factors

Not outlined
Unclear/Unable to assess 10. The nature of the causal pathway between the intervention and the outcome it is intended to effect

Not outlined
Unclear/Unable to assess Study ID: Cormack 1994 Study title: Evaluation of an easy, cost-effective strategy for cutting benzodiazepine use in general practice

Study and Intervention details
Study aims/objectives "to assess the effect of a letter from the general practitioner, suggesting a reduction in the use of benzodiazepines, and whether the impact of the letter could be increased by the addition of information on how to tackle drug reduction." Study outcome(s) "to try to reduce or stop their benzodiazepine medication" Details of intervention/s and the comparison (including usual care) Intervention Group 1 : "received a letter from their general practitioner asking them to try to reduce or stop their benzodiazepine medication and advising that this should be done gradually (Appendix 1)" Intervention Group 2: "received the same letter, followed at monthly intervals by four information sheets giving advice about reducing medication, including practical suggestions for coping without drugs." Control Group: "received no intervention" Intervention aim/objectives "to try to reduce or stop their benzodiazepine medication" Intervention deliverer GPs -"received a letter from their general practitioner asking them to try to reduce or stop their benzodiazepine medication and advising that this should be done gradually" Intervention target/recipient (which may include individuals, groups of individuals and other entities) "Long-term users were identified by general practitioners and divided into three groups: two intervention groups and a control group" Target behaviour and component actions (i.e. whose behaviour the intervention intended to change and what were the component actions involved in that behaviour) Not much detail given. The target behaviour was "reduction of benzodiazepine use"

Intervention Group 1: Core dimension
Description of the intervention in the review Judgement Support for judgement

Organisational levels and categories targeted by the intervention
"long-term users of benzodiazepines in general practice were divided into three groups: two intervention groups and a control group."

Single category
Only patients being targeted by intervention.

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"reduction of benzodiazepine use"

Single target
Only one behaviour targetedreduction in benzodiazepine consumption 3. Active components included in the intervention, in relation to the comparison "The first intervention group received a letter One component Only one component to from their general practitioner asking that benzodiazepine use be gradually reduced and perhaps, in time, stopped." the interventiona letter from the patients GP 4. The degree of tailoring intended or flexibility permitted across sites or individuals in applying or implementing the intervention "Those in intervention group one received a letter from their general practitioner asking them to try to reduce or stop their benzodiazepine medication and advising that this should be done gradually (Appendix 1)."

Inflexible
Same letter was given to all the patientsno tailoring.

The level of skill required by those delivering the intervention in order to meet the intervention's objectives
Not explicitly mentioned in text -"received a letter from their general practitioner asking that benzodiazepine use be gradually reduced and perhaps, in time, stopped" Doctors likely had to support patients in reducing benzodiazepine consumption. .

Intermediate level skills
Intermediate level skills required to support BENZODIAZEPI NE withdrawal.

The level of skill required for the targeted behaviour when entering the included studies by those receiving the intervention, in order to meet the intervention's objectives
Not explicitly stated in the report -high level skills required to undergo successful benzodiazepine discontinuation High level skills High level skill to undergo benzodiazepine discontinuation successfully.

Judgement Support for judgement 7. The degree of interaction between intervention components, including the independence / interdependence of intervention components
Not outlined Unclear/Unable to assess

The degree to which the effects of the intervention are dependent on the context or setting in which it is implemented
Not outline Unclear/Unable to assess 9. The degree to which the effects of the intervention are modified by recipient or provider factors

Not outlined
Unclear/Unable to assess

Not outlined
Unclear/Unable to assess Intervention Group 2 Core dimension Description of the intervention in the review Judgement Support for judgement 1. Organisational levels and categories targeted by the intervention "long-term users of benzodiazepines in general practice were divided into three groups: two intervention groups and a control group."

Single category
Only patients being targeted by intervention.

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"reduction of benzodiazepine use"

Single target
Only one behaviour targetedreduction in benzodiazepine consumption

Active components included in the intervention, in relation to the comparison
Intervention group two received the same letter, followed at monthly intervals by four information sheets giving advice about reducing medication, including practical suggestions for coping without drugs.
More than one component and delivered as a bundle The letter preceded the information sheetstherefore components were delivered as a bundle.

The degree of tailoring intended or flexibility permitted across sites or individuals in applying or implementing the intervention
"Intervention group two received the same letter, followed at monthly intervals by four information sheets giving advice about reducing medication, including practical suggestions for coping without drugs" Inflexible Same letter and information sheets received by all patientsno tailoring of intervention.

The level of skill required by those delivering the intervention in order to meet the intervention's objectives
Not explicitly mentioned in text. Doctors likely had to support patients in reducing benzodiazepine consumption. .

Intermediate level skills
Intermediate level skills required to support BENZODIAZEPI NE withdrawal.

The level of skill required for the targeted behaviour when entering the included studies by those receiving the intervention, in order to meet the intervention's objectives
Not explicitly stated in the report -high level skills required to undergo successful benzodiazepine discontinuation High level skills High level skill to undergo benzodiazepine discontinuation successfully. Study aims/objectives "to appraise the efficacy of a structured intervention in primary care, consisting of a brief standardised advice and a stepwise dose reduction, for discontinuing benzodiazepine use" Study outcome(s) "The main efficacy variable was benzodiazepine use at 12 months, although data was also taken at 6 months" Details of intervention/s and the comparison (including usual care) "The intervention consisted of an interview with a standardised message that had been developed previously through a qualitative study on four focal groups, each one with eight to 12 chronic consumers of benzodiazepines (one group of men and three of women, grouped per age). The content of the message is given in Box 1. Patients in the intervention group underwent a gradual reduction of benzodiazepine dose, with control visits every 15 days. The dose was reduced between 10 and 25% of the initial dose fortnightly. For patients in the control group, the same information was taken on personal, clinical, benzodiazepine use and psychological tests. They did not receive the structured intervention, being managed according to usual practice, and informed of the convenience of reducing the use of benzodiazepines" Intervention aim/objectives "withdrawal of long-term benzodiazepine use"

Optional dimension Description of the intervention in the review
Intervention deliverer Physicians -"Thirteen family physicians from three primary care centres took part in the trial." Intervention target/recipient (which may include individuals, groups of individuals and other entities) "patients visiting the collaborating physicians, those aged 14-75 years and who were taking benzodiazepines at least five times a week for over a year," Target behaviour and component actions (i.e. whose behaviour the intervention intended to change and what were the component actions involved in that behaviour) "withdrawal of long-term benzodiazepine use"

Core dimension
Description of the intervention in the review Judgement Support for judgement

Organisational levels and categories targeted by the intervention
"patients visiting the collaborating physicians, those aged 14-75 years and who were taking benzodiazepines at least five times a week for over a year," Single category Intervention was only targeted at patients.

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"withdrawal of long-term benzodiazepine use"

Single target
Only one behaviour targeted by the interventionbenzodiazepine use.

Active components included in the intervention, in relation to the comparison
"intervention consisted of an interview with a More than one component and The intervention

Judgement Support for judgement 7. The degree of interaction between intervention components, including the independence / interdependence of intervention components
Not outlined Unclear/Unable to assess

The degree to which the effects of the intervention are dependent on the context or setting in which it is implemented
Not outline Unclear/Unable to assess

The degree to which the effects of the intervention are modified by recipient or provider factors
Not outlined Unclear/Unable to assess

Not outlined
Unclear/Unable to assess Study aims/objectives "evaluated the impact of direct-to-patient education, with or without a pharmacist consultation, on Z-drug discontinuation among Kaiser Permanente Northwest members age 64 years and older." Study outcome(s) "The primary study outcome was discontinuation of Z-drugs during 6-month follow-up, defined as a patient not receiving a Zdrug dispensing from a KPNW pharmacy during that time." "secondary outcomes, which included hospitalization, outpatient face-to-face encounters, and urgent care and Emergency Department visits during the 6-month follow-up. We also examined the number of Z-drug dispensing during follow-up for patients who did not discontinue use." Details of intervention/s and the comparison (including usual care) Group 1: Education Only "received a letter from their prescribing physician, an educational brochure, and a quiz. Educational materials were developed by a team of primary care and geriatric health care physicians, pharmacists, and researchers. Prescriber letter text explained the reason for the letter and encouraged patients to reconsider their Z-drug use. The brochure presented evidence of Z-drug-induced harms, suggestions for effective pharmacologic and nonpharmacologic alternatives to treat insomnia, and a visual tapering schedule with further instructions. The quiz reiterated messages in the educational brochure by providing a selfassessment about Z-drug use risks" Group 2: Education and Arms As above + "A pharmacist called patients in the Ed+ study arm 2 to 4 weeks after they received the educational materials. During these telephone consultations, the pharmacist would discuss and reinforce information in the educational mailing; assess patient barriers to Z-drug discontinuation; provide personalized guidance on tapering, recommendations for care coordination opportunities available through specialty departments such as sleep medicine, mental health, and addiction medicine; and answer questions. This format also provided the opportunity to discuss Z-drug alternatives, including sleep hygiene techniques and safer medications. The pharmacist had prescriber approval and a protocol that allowed for a switch to safer sleep medications" Intervention aim/objectives Z-drug discontinuation Intervention deliverer Group 1: GP Group 2: Pharmacists and GPs "A pharmacist called patients in the Ed+ study arm 2 to 4 weeks after they received the educational materials." "received a letter from their prescribing physician" Intervention target/recipient (which may include individuals, groups of individuals and other entities) "Patients were eligible for the deprescribing intervention if they were at least age 64 years and received 2 or 3 prescription medication dispensing's of a Z-drug-including eszopiclone, zolpidem, or zaleplon-during 2016" Target behaviour and component actions (i.e. whose behaviour the intervention intended to change and what were the component actions involved in that behaviour) Z-drug use "engage them in shared decision making regarding discontinuation"

Ed Group Core dimension
Description of the intervention in the review Judgement Support for judgement

Organisational levels and categories targeted by the intervention
"Patients were eligible for the deprescribing intervention if they were at least age 64 years and received 2 or 3 prescription medication dispensing of a Z-drugincluding eszopiclone, zolpidem, or zaleplonduring 2016"

Single category
Only patients are targeted by the intervention.

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"engage them in shared decision making regarding discontinuation"

Single target
One behaviour targeted -zdrug discontinuation

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"engage them in shared decision making regarding discontinuation"

Single target
One behaviour targeted -zdrug discontinuation

The level of skill required for the targeted behaviour when entering the included studies by those receiving the intervention, in order to meet the intervention's objectives
Not explicitly stated in the report -high level skills required to undergo successful benzodiazepine discontinuation High level skills High level skill to undergo benzodiazepine discontinuation successfully.

Judgement Support for judgement 7. The degree of interaction between intervention components, including the independence / interdependence of intervention components
Not outlined Unclear/Unable to assess

The degree to which the effects of the intervention are dependent on the context or setting in which it is implemented
Not outline Unclear/Unable to assess 9. The degree to which the effects of the intervention are modified by recipient or provider factors

Not outlined
Unclear/Unable to assess

Not outlined
Unclear/Unable to assess Study ID: Navy 2018 Study title: Clinical Pharmacist Intervention to Engage Older Adults in Reducing Use of Alprazolam

Study and Intervention details
Study aims/objectives "to assess whether an educational letter explaining the risks of alprazolam can provide an impetus for older adults to call a clinical pharmacist to participate more actively in their own health care and engage in benzodiazepine use reduction" Study outcome(s) "the primary outcome was a comparison between the intervention and control groups on the composite rate of patients who 1) had no alprazolam dispensing at any time during the six month follow up, 2) had an alprazolam dose reduction at any time during the six-month follow-up, or 3) interchanged to an alternate medication at any time during the six-month follow up" "secondary outcomes included comparisons between the groups on the individual outcomes of the composite and rate of intervention patients who called the study CP within 14 days of the study letter being mailed" Details of intervention/s and the comparison (including usual care) "An intervention letter |(appendix) was developed with input from the KPCO geriatric CPs and the medical director of geriatrics and Medicare. The letter was addressed to the patient and outlined: 1) the reason for it being sent (i.e., the patient was prescribed alprazolam), 2) that there are risks to taking alprazolam, 3) organisations that recommend against taking alprazolam, 4) alprazolam's side effects, 5) possible alternate treatment options, 6) a request to call the study CP to discuss treatment options, 7) not to stop taking alprazolam without talking to the study CP, and 8) the telephone number and times to call the study" "letters were sent via the US postal service on a rolling basis to allow the study CP to manage telephone calls and use-reduction efforts, if a patient called the study CP, usual care was provided. During the usual care discussion, the study CP assessed the patients decisional capacity to understand and follow instructions. If the patient could not comprehend the information provided or make a reasoned choice regarding alprazolam dose reduction or discontinuation, the study CP did not proceed with study…" "for patients who agreed to participate, alternate treatment options were discussed on a case-by-case basis…" "if the patient was agreeable, the study CP collaborated with the patient's primary care provider (PCP) to develop an individualised alprazolam taper plan. The study CP would monitor the patient for withdrawal symptoms by telephone follow-up throughout the duration of the taper. For patients who did not agree to study participation, usual care was provided" Intervention aim/objectives "provide an impetus for older adults to call a clinical pharmacist to participate more actively in their own health care and engage in benzodiazepine use reduction" Intervention deliverer Clinical pharmacist Intervention target/recipient (which may include individuals, groups of individuals and other entities) "patients were included if they were 65 years of age or older as of December 15 2016, continuous members of KPCO for the 3 months prior, members from the Denver/ Boulder metropolitan area who resided at home, had a current supply of alprazolam as of December 15, 2017, and had four outpatient dispensings of alprazolam during the previous 12 months with a total of at least 90 days of medication supplied" Target behaviour and component actions (i.e. whose behaviour the intervention intended to change and what were the component actions involved in that behaviour) "provide an impetus for older adults to call a clinical pharmacist to participate more actively in their own health care and engage in benzodiazepine use reduction"

Core dimension
Description of the intervention in the review Judgement Support for judgement

Organisational levels and categories targeted by the intervention
"patients were identified for study participation from pharmacy dispensing records" Single category Intervention only targets patients

Behaviour or actions of intervention recipients or participants to which the intervention is directed
"provide an impetus for older adults to call a clinical pharmacist to participate more actively in their own health care and engage in benzodiazepine use reduction"

Single target
Only one behaviour targetedbenzodiazepine use.

Not outlined
Unclear/Unable to assess

The degree to which the effects of the intervention are dependent on the context or setting in which it is implemented
Not outline Unclear/Unable to assess 9. The degree to which the effects of the intervention are modified by recipient or provider factors

Not outlined
Unclear/Unable to assess

The nature of the causal pathway between the intervention and the outcome it is intended to effect
Not outlined Unclear/Unable to assess Study ID: Vicens 2014 Study title: Comparative efficacy of two interventions to discontinue long-term benzodiazepine use: cluster randomised controlled trial in primary care

Study and Intervention details
Study aims/objectives "This study assessed two interventions: a structured educational intervention with gradual tapering backed up by fortnightly follow-up visits (SIF) and the same structured educational intervention supported by written instruction rather than followup visits (SIW), requiring less GP involvement.
The aim was to compare the effectiveness of these two interventions with that of usual care on the discontinuation of long-term benzodiazepine use in primary care patients, delivered at the level of the GP. We also attempted to determine the effectiveness of each intervention relative to patient characteristics." Study outcome(s) "The primary outcome was benzodiazepine discontinuation at 12 months, assessed in a personal interview and defined as selfdeclared non-consumption or consumption of fewer than four doses in the previous month. Consumption was reviewed and confirmed by prescription claims in the clinical records." "Secondary outcomes were benzodiazepine discontinuation at 6 months and safety outcomes measured at 6 months and 12 months, including changes in anxiety and depression symptoms, changes in sleep satisfaction, alcohol consumption and withdrawal symptoms." Details of intervention/s and the comparison (including usual care) Both groups: "Practitioners assigned to the SIF and SIW groups attended a supplementary 3 h workshop on structured interviews, individualised patient information and training in managing benzodiazepine discontinuation and optimal gradual dose reduction. In addition, GPs assigned to the SIF group attended a brief 30 min workshop to standardise the dose-reduction followup visits. Training was provided by researchers with extensive experience in the management of benzodiazepine withdrawal. The SIF and SIW interventions were both based on a structured educational interview and GP-tailored stepped benzodiazepine dose reduction. These two interventions differed only in the follow-up" SIF: "The content of the educational interview was structured and included four key points: (a) information on benzodiazepine dependence, abstinence and withdrawal symptoms; (b) the risks of long-term use, memory and cognitive impairment, accidents and falls; (c) reassurance about reducing medication; (d) a selfhelp leaflet to improve sleep quality if patients were taking benzodiazepines for insomnia Practitioners assigned to the SIF and SIW groups attended a supplementary 3 h workshop on structured interviews, individualised patient information and training in managing benzodiazepine discontinuation and optimal gradual dose reduction. In addition, GPs assigned to the SIF group attended a brief 30 min workshop to standardise the dose-reduction followup visits. Training was provided by researchers with extensive experience in the management of benzodiazepine withdrawal. The SIF and SIW interventions were both based on a structured educational interview and GP-tailored stepped benzodiazepine dose reduction. These two interventions differed only in the follow-up. The content of the educational interview was structured and included four key points: (a) information on benzodiazepine dependence, abstinence and withdrawal symptoms; (b) the risks of long-term use, memory and cognitive impairment, accidents and falls; (c) reassurance about reducing medication; (d) a self-help leaflet to improve sleep quality if patients were taking benzodiazepines for insomnia" After the first intervention visit patients in the SIF group were scheduled for follow-up appointments with their GPs every 2-3 weeks until the end of the dose reduction. The GPs reinforced education, reassured patients regarding withdrawal symptoms and obtained patient agreement for the next step in dose reduction." SIW: "Patients in the SIW group received written instructions reinforcing educational information at their first and only contact with their GP, along with a tailored gradual dose reduction until benzodiazepine cessation. No follow-up visit was scheduled, although patients could spontaneously request an appointment with their GP when needed." Control: "Patients allocated to the control group received routine care; their GPs could provide brief advice but did not receive any specific recommendation about the management of long-term benzodiazepine use from the study trainers." Intervention aim/objectives "self-declared benzodiazepine discontinuation confirmed by prescription claims at 12 months" Intervention deliverer GPs -"Participating GPs were selected from 21 primary care centres in the three regions and were included if they were able to commit to taking part until completion" Intervention target/recipient (which may include individuals, groups of individuals and other entities) Patients eligible for the trial were aged 18-80 years and had been taking benzodiazepines daily for at least 6 months. Exclusion criteria were psychotic or personality disorder, or current treatment by a psychiatrist; severe anxiety, depressive disorder or severe medical illness including dementia and epilepsy as clinically assessed by the GP, or in cases where they considered that stopping benzodiazepine might be harmful; alcohol or illicit drug misuse; patient in residential care or terminally ill; inability to read and speak Spanish; or unwillingness to provide informed consent Target behaviour and component actions (i.e. whose behaviour the intervention intended to change and what were the component actions involved in that behaviour) "benzodiazepine discontinuation at 12 months"

Core dimension
Description of the intervention in the review Judgement Support for judgement

Organisational levels and categories targeted by the intervention
"Patients eligible for the trial were aged 18-80 years and had been taking benzodiazepines daily for at least 6 months." Single category Intervention only targeted patients.

Behaviour or actions of intervention recipients or participants to which the intervention is directed
""benzodiazepine dose reduction" Single target Only one behaviour being targeted benzodiazepine use. optimal gradual dose reduction. In addition, GPs assigned to the SIF group attended a brief 30 min workshop to standardise the dose-reduction followup visits. Training was provided by researchers with extensive experience in the management of benzodiazepine withdrawal"

Active components included in the intervention, in relation to the comparison
6. The level of skill required for the targeted behaviour when entering the included studies by those receiving the intervention, in order to meet the intervention's objectives Not explicitly stated in the report -high level skills required to undergo successful benzodiazepine discontinuation High level skills High level skill to undergo benzodiazepine discontinuation successfully.

Not outlined
Unclear/Unable to assess

The degree to which the effects of the intervention are dependent on the context or setting in which it is implemented
Not outline Unclear/Unable to assess 9. The degree to which the effects of the intervention are modified by recipient or provider factors "Withdrawal at 12 months did not differ by gender, age, short or long halfdepression (HADS score), insomnia (Oviedo questionnaire) or degree of dependence (SDS). benzodiazepine use,"

Largely independent of individual-level factors -
Effect of intervention was not impacted by patient characteristics.

The nature of the causal pathway between the intervention and the outcome it is intended to effect
Not outlined -Unclear/Unabl e to assess

SIW Group
Core dimension Description of the intervention in the review Judgement Support for judgement 1) Organisational levels and categories targeted by the intervention "Patients eligible for the trial were aged 18-80 years and had been taking benzodiazepines daily for at least 6 months." Single category Intervention only targeted patients.
2) Behaviour or actions of intervention recipients or participants to which the intervention is directed ""benzodiazepine dose reduction" Single target Only one behaviour being targeted benzodiazepine use.

3) Active components included in the intervention, in relation to the comparison
"Practitioners assigned to the SIF and SIW groups attended a supplementary 3 h workshop on structured interviews, individualised patient information and training in managing benzodiazepine discontinuation and optimal gradual dose reduction. …The SIF and SIW interventions were both based on a structured educational interview and GP-tailored stepped benzodiazepine dose reduction. These two interventions differed only in the follow-up. "Patients in the SIW group received written instructions reinforcing educational information at their first and only contact with their GP, along with a tailored gradual dose reduction until benzodiazepine cessation. No follow-up visit was scheduled, although patients could spontaneously request an appointment with their GP when needed."

More than one component and delivered as a bundle
Intervention consists of a number of different components which were delivered in a specific orderinterview with GP preceded written instructions.

4) The degree of tailoring intended or flexibility permitted across sites or individuals in applying or implementing the intervention
Practitioners assigned to the SIF and SIW groups attended a supplementary 3 h workshop on structured interviews, individualised patient information and training in managing benzodiazepine discontinuation and optimal gradual dose reduction Moderately tailored/flexible Interviews were tailored based on patient information 5) The level of skill required by those delivering the intervention in order to meet the intervention's objectives "General practitioners assigned to the three groups attended an hour-

Intermediate level skills -
GPs had to undergo a number of